P1152: DEPTH OF METABOLIC RESPONSE AT INTERIM PET AND SURVIVAL OUTCOMES AMONG PATIENTS WITH PRIMARY REFRACTORY OR EARLY RELAPSING DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)
Authors: Allison Bock, Raphael Mwangi, Fatemeh Ataei, Matthew Thorpe, Matthew Maurer, Josh Pritchett, Jacob Shreve, Jonas Paludo, James Cerhan, Arushi Khurana, Thomas Witzig, Thomas Habermann, Yucai Wang, Grzegorz S. Nowakowski, Jason Young
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Identifying patients with DLBCL at high risk for frontline (1L) treatment failure or early relapse is challenging. Total metabolic tumor volume (TMTV) and maximum standardized uptake value (SUVmax) may improve upon standard 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)-based assessment during treatment. Aims: We report the association of TMTV and SUVmax response by interim PET (PET2) on survival outcomes in patients with primary refractory DLBCL (prDLBCL) and early relapsing DLBCL (erDLBCL). Methods: Adult patients with prDLBCL (less than a complete response at EOT or progression during treatment) or erDLBCL (CR at EOT with a relapse within 12 months) between 2005 and 2019 and seen at Mayo Clinic Rochester were included. The % change (Δ) from baseline to PET2 (after 2 cycles of 1L immunochemotherapy) of TMTV and maximum SUV uptake (SUVmax) were measured. A PET segmentation threshold of 1.5 liver mean SUV + two standard deviations with a minimum volume constraint of 0.5 mL was utilized (MIM Software, Inc., Cleveland OH, USA) with manual input as needed. Functional spline analysis showed a ΔSUVmax decline ≥65% and a ΔTMTV decline ≥75% at PET2 were associated with improved OS and determined threshold for further analysis. Results: 131 patients with prDLBCL or erDLBCL, 131 had complete PET-CT data available (N=79 prDLBCL, N=52 erDLBCL). Median baseline TMTV was 939.5 cm3 (range 13.1-6840.4) in prDLBCL and 670.4 cm3 (0.9-5464.5) in erDLBCL (p=0.01). Baseline median SUVmax was 22.2 (3.1-52.6) in prDLBCL and 19.1 (2.0-49.7) in erDLBCL (p=0.02). The 2-year estimated OS rate was 21% (95% CI: 13-34) for prDLBCL and 58% (95% CI: 45-75) for erDLBCL. At a median follow up of 77.6 months, 81 patients had died. Among all patients, Two-year OS rate was 53% (95% CI: 42-67) for patients with a PET2 ΔSUVmax decline ≥65% compared to 15% (95% CI: 7-29) for patients with a PET2 ΔSUVmax decline <65%(p<0.001)(Fig. A). PrDLBCL had a 2-year OS rate of 48% (95% CI: 31-74) for a ΔSUVmax ≥65% compared to 7% (95% CI: 2-21) for patients with a ΔSUVmax <65%(p<0.001)(Fig. B), which captured 58% of prDLBCL patients (N=46). Among all patients, 2-year OS rate was 43% (95% CI: 34-54) for patients with a ΔTMTV ≥75% compared to 5% (95% CI: 1-35) for patients with a ΔTMTV <75% (p<0.001)(Fig. C). All patients with a ΔTMTV <75% had prDLBCL. PrDLBCL had a 2-year OS rate of 28% (95% CI: 18-44) for a ΔTMTV ≥75%(Fig. D). The outcomes for ΔSUVmax <65% and ΔTMTV <75% at PET2 remained significant in a cox model when adjusted for IPI and bulky disease (>10cm). Summary/Conclusion: A ΔTMTV decline <75% or a ΔSUVmax decline <65% at PET2 identified an ultra-high-risk subgroup of prDLBCL with particularly poor outcomes, that was still significant after adjusting for IPI and bulky baseline disease. These patients may benefit from alternative PET-adapted treatment strategies, but further evaluation among all patients with DLBCL is needed. Figure 1. Overall survival among A) all patients with a PET2 ΔSUVmax threshold of 65% B) ΔSUVmax stratified by prDLBCL or early relapsing DLBCL and C) all patients with a ΔTMTV threshold of 75% D) ΔTMTV stratified by prDLBCL or early relapsing DLBCL.Keywords: DLBCL, Refractory, NHL, Chemorefractory